Pyrido[1,5]benzodiazepinone derivatives and pharmacological activities thereof

ABSTRACT

11-Acyl derivatives of 5,11-dihydro-6H-pyrido-[2,3-b][1,4]benzodiazepin-6-one, 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one and 5,11-dihydro-6H-benzo[2,3-b][1,4]benzodiazepin-6-one, their preparation and pharmaceutical compositions endowed with antisecretory, antiulcer, antimuscarinic, spasmolytic activities containing the same, are described.

The present invention refers to new compounds having general formula I##STR1## wherein Y is N or a CH group, A is NH and B is C═O or C═S orvice versa, R represents a group of formula ##STR2## wherein:

R₁ represents hydrogen or C₁ -C₄ linear or branched alkyl,

n is 0, 1 or 2.

When n is 0, M represents one of the following nitrogen cyclic groups:##STR3##

When n is 1 or 2, M is a group of formula: ##STR4## wherein, when n is 1and R₁ is hydrogen, R₂ represents hydrogen or C₁ -C₄ linear or branchedalkyl and R₃ is chosen among one of the following groups: --CH₂--CH═CH₂, --CH₂ --C.tbd.CH, CH₂ --CH₂ --CN, ##STR5## or R₂ and R₃, takentogether, form one of the following cyclic residues: ##STR6## wherein R₄is hydrogen, methyl or ethyl;

R₅ is --COOH, --COOCH₃, --COOC₂ H₅ or ##STR7##

R₆ is acetyl, phenyl, cyclopropyl, CH₂ --CH₂ OH, CH₂ --CH₂ --CH₂ OH,##STR8## --COOC₂ H₅ or ##STR9## R₇ is hydrogen or methyl.

When n is 1 and R₁ is, on the other hand, C₁ -C₄ alkyl, R₂ and R₃,separately, have the above mentioned meanings and, taken together, mayform one of the following cycles: ##STR10## wherein R₄ has the abovementioned meaning.

Lastly, when n is 2, R₁ has the above mentioned meanings, R₂ may behydrogen or methyl and R₃ represents one of the following groups:##STR11## or R₂ and R₃, taken together, form one of the following cyclicresidues: ##STR12## wherein R₄ has the above mentioned meanings.

The compounds of formula I are endowed with interestingpharmaco-therapeutic properties, namely with antisecretory, antiulcer,spasmolytic and antimuscarinic activities. The invention thereforerefers also to pharmaceutical compositions containing as the activeprinciple one or more compounds of formula I or their pharmaceuticallyacceptable salts.

The invention refers also to a process for the preparation of thecompounds of formula I.

Compounds I having n equal to to 0 are prepared starting from thecompounds of formula II, described in the German Pat. No. 1,179,943, inBull. Soc. Chim. Fran. 7, 2316, 1966 and in J. Med. Chem. 6, 255, 1963,by acylation with the acyl chlorides of formula III, according to thefollowing scheme I: ##STR13##

In the Scheme I, A, B, Y, M have the above mentioned meanings: M, whenn=0, represents therefore the following groups: ##STR14##

The reaction is carried out in polar solvents such as dimethylformamide,dimethylsulfoxide in the presence of bases such as triethylamine,alkaline hydroxides, alkaline carbonates at temperatures ranging fromthe room temperature and 150° C., with reaction times ranging from 2 to24 hours.

The compounds I wherein n is, on the other hand, 1 or 2, are prepared byreaction of the chloroacyl derivatives IV, described in the German Pat.Nos. 1,795,183 and 2,724,478, in the French Pat. No. 1,505,795 and in J.Med. Chem. 6, 255, 1963 with amines of formula ##STR15## according tothe following Scheme II: ##STR16##

In the reported scheme, A, B, Y, n, R₁, R₂ and R₃ have the above seenmeanings while X is an halogen atom.

The reaction is carried out in solvents such as benzene, alcohols,dioxane, etc. at temperatures ranging from the room temperature to thereflux temperature of the used solvent. As hydrohalogen acid bindingbase the amine V itself, an alkaline carbonate, triethylamine etc., maybe used.

The reaction times are usually ranging from 2 to 24 hours.

The following examples further illustrate the invention, withoutlimiting in any way the scope thereof.

EXAMPLE 111-[2-(Piperidin-1-yl)propionyl]-5,11-dihydro-6H-pyrido-[2,3-b][1,4]benzodiazepin-6-one

A suspension of11-(2-chloropropionyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one(10 g) and piperidine (5.65 g) in benzene (350 ml) was refluxed withstirring for 20 hours. The reaction mixture was then cooled to roomtemperature and filtered, washing the collected solid with water.

Crystallization from 95° ethanol yielded 3.5 g (30.2%) of11-[2-(piperidin-1-yl)propionyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-onemelting at 238°-240° C. (dec.).

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            68.55    68.82                                                   H             6.33     6.47                                                   N            15.99    16.14                                                   ______________________________________                                    

EXAMPLE 211-[2-(Hexamethylenimino)acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

A suspension of11-(2-chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one(15 g) and hexamethylenimine (10.34 g) in benzene (400 ml) was refluxedunder stirring for 20 hours. The reaction mixture was then cooled toroom temperature and filtered washing with water the collected solid.Crystallization from 95° ethanol yielded 8 g (43.8%) of11-[2-(hexamethylenimino)acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-onemelting at 199°-200° C.

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            68.55    68.33                                                   H             6.33     6.54                                                   N            15.99    15.75                                                   ______________________________________                                    

EXAMPLE 311-(1-Methylpiperidin-4-carbonyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

The chloride of 1-methylpiperidine-4-carboxylic acid hydrochloride (4.7g) was added to a solution of5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (5 g) andtriethylamine (7.5 ml) in dimethylformamide (200 ml). The reactionmixture was heated to 90° C. for 24 hours.

The solvent was evaporated under vacuum and the residue was dissolved in10% acetic acid (150 ml). The solution was repeatedly washed withmethylene chloride, decolored with charcoal, alkalinized to pH 8 withsaturated solution of sodium bicarbonate and extracted with methylenechloride (100 ml×5). The collected organic extracts were dried on sodiumsulphate and evaporated. The residue, crystallized fromethanol-ethylether, yielded 2.4 g (30%) of11-(1-methylpiperidin-4-carbonyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-onemelting at 265°-267° dec.

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            67.84    67.81                                                   H             5.99     6.08                                                   N            16.65    16.53                                                   ______________________________________                                    

EXAMPLE 411-[3-(Hexamethylenimino)propionyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

A suspension of11-(3-chloropropionyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one(4.5 g) and hexamethylenimine (3.37 ml) in dioxane (50 ml) was refluxedunder stirring for two hours. The reaction mixture was then cooled toroom temperature and filtered. The collected solid was crystallized from95° ethanol to give 3 g (55%) of11-[3-(hexamethylenimino)propionyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-onemelting at 217°-218° C.

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            69.21    69.42                                                   H             6.64     6.73                                                   N            15.37    15.20                                                   ______________________________________                                    

EXAMPLE 511-[2-(2-Methylpiperidin-1-yl)acetyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one

A suspension of11-(2-chloroacetyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one(2.9 g) and 2-methylpiperidine (2.37 ml) in dioxane (30 ml) was refluxedunder stirred for two hours. After cooling and filtration, the collectedsolid was crystallized from absolute ethanol to give 1.3 g (37.2%) of11-[2-(2-methylpiperidin-1-yl)acetyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-onemelting at 248°-249° C. (dec.).

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            68.55    68.35                                                   H             6.33     6.17                                                   N            15.99    15.68                                                   ______________________________________                                    

EXAMPLE 611-[2-(4-Methylpiperazin-1-yl)acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-thione

A suspension of11-[2-(4-methylpiperazin-1-yl)acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-onedihydrochloride (10.6 g) and phosphorus pentasulfide (6.1 g) in pyridine(125 ml) was refluxed under stirring for 7 hours.

After cooling and filtration, the collected solid was suspended inchloroform (500 ml) and the suspension was repeatedly washed withsaturated solution of sodium bicarbonate until disappearance of solid insuspension. The organic phase was dried on sodium sulphate andevaporated. The residue, crystallized first from acetonitrile and thenfrom methanol, yielded 2.7 g (30%) of11-[2-(4-methylpiperazin-1-yl)acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-thionemelting at 240°-241° C.

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            62.10    62.32                                                   H             5.76     5.84                                                   N            19.06    19.06                                                   ______________________________________                                    

EXAMPLE 711-[2-[4-(3-Hydroxypropyl)piperazin-1-yl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

1-Piperazinepropanol (8 g) was added to a suspension of11-(2-chloroacetyl)-5,11-dihydro-6H-pyrido-[2,3-b][1,4]benzodiazepin-6-one(15 g) and anhydrous sodium carbonate (15 g) in absolute ethanol (250ml).

The mixture was refluxed under stirring for 6 hours and then cooled. Thesalts were removed by filtration. The clear solution was evaporated todryness and the residue, crystallized from acetonitrile, yielded 8.5 g(41%) of11-[2-[4-(4-hydroxypropyl)piperazin-1-yl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-onemelting at 215°-216° C.

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            63.78    63.62                                                   H             6.37     6.41                                                   N            17.70    17.64                                                   ______________________________________                                    

EXAMPLE 811-(2-Chlorobutirryl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepin-6-on

2-Chlorobutirryl chloride (72.2 ml) was added to a suspension of5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (100 g) andtriethylamine (107 ml) in dioxane (1.9 lt.). The mixture was refluxedunder stirring for 6 hours and then filtered still boiling. The filtratewas evaporated to dryness and the residue, crystallized fromacetonitrile, yielded 60 g (40.2%) of11-(2-chlorobutirryl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-onemelting at 207°-209° C.

    ______________________________________                                        Microanalysis                                                                            Calc. %                                                                              Found %                                                     ______________________________________                                        C            60.86    60.84                                                   H             4.47     4.47                                                   N            13.31    13.28                                                   ______________________________________                                    

EXAMPLES 9-52

Similarly to the previously described methods, but starting from thesuitable intermediates, the compounds 9-52, whose formulae andchemico-physical characteristics are reported in the following Tables,were obtained.

                                      TABLE I                                     __________________________________________________________________________     ##STR17##                                                                                                      Microanalysis                               Compound                 Yield                                                                             M.p. Calc. %  Found %                            n.    R                  %   °C.                                                                         C  H  N  C  H  N                            __________________________________________________________________________     9                                                                                   ##STR18##         45  156-158                                                                            64.47                                                                            5.11                                                                             20.88                                                                            64.36                                                                            5.04                                                                             20.70                        10                                                                                   ##STR19##         31  207-208                                                                            69.2                                                                             6.64                                                                             15.37                                                                            69.08                                                                            6.43                                                                             15.32                        11                                                                                   ##STR20##         36  312-313                                                                            63.21                                                                            6.63                                                                             15.36                                                                            63.09                                                                            6.73                                                                             15.16                        12                                                                                   ##STR21##         29  212-214                                                                            62.98                                                                            6.08                                                                             18.36                                                                            62.78                                                                            5.90                                                                             18.16                        13                                                                                   ##STR22##         24  184-186                                                                            61.3                                                                             6.12                                                                             17.02                                                                            61.36                                                                            6.18                                                                             17.09                        14                                                                                   ##STR23##         28  284-286                                                                            63.31                                                                            5.58                                                                             1.46                                                                             63.38                                                                            5.71                                                                             18.22                        15                                                                                   ##STR24##         51  213-214                                                                            61.60                                                                            5.66                                                                             17.10                                                                            61.86                                                                            5.72                                                                             17.11                        16                                                                                   ##STR25##         30  275  69.71                                                                            5.61                                                                             16.94                                                                            69.59                                                                            5.68                                                                             16.88                        17                                                                                   ##STR26##         33  202-203                                                                            65.39                                                                            6.20                                                                             13.26                                                                            65.42                                                                            6.27                                                                             13.30                        18                                                                                   ##STR27##         28  224-226                                                                            68.95                                                                            5.79                                                                             16.08                                                                            68.96                                                                            5.78                                                                             16.08                        19                                                                                   ##STR28##         20  188-189                                                                            69.82                                                                            6.92                                                                             14.80                                                                            69.66                                                                            6.87                                                                             14.77                        20                                                                                   ##STR29##         24  207-209                                                                            67.50                                                                            6.44                                                                             17.89                                                                            67.60                                                                            6.45                                                                             17.86                        21                                                                                   ##STR30##         33  205-207                                                                            68.55                                                                            6.33                                                                             15.99                                                                            68.37                                                                            6.52                                                                             15.83                        22                                                                                   ##STR31##         57  224-226                                                                            67.84                                                                            5.99                                                                             16.65                                                                            67.91                                                                            6.02                                                                             16.58                        23                                                                                   ##STR32##         57  208-210                                                                            67.21                                                                            5.43                                                                             17.42                                                                            67.17                                                                            5.48                                                                             17.4                         24                                                                                   ##STR33##         26  217-218                                                                            55.76                                                                            6.01                                                                             15.48                                                                            55.74                                                                            5.98                                                                             15.47                        25                                                                                   ##STR34##         35  238-239                                                                            69.21                                                                            6.64                                                                             15.37                                                                            69.11                                                                            6.60                                                                             15.35                        26                                                                                   ##STR35##         21  201-202                                                                            69.21                                                                            6.64                                                                             15.37                                                                            69.25                                                                            6.70                                                                             15.43                        27                                                                                   ##STR36##         22  183-184                                                                            67.84                                                                            5.99                                                                             16.65                                                                            67.90                                                                            5.91                                                                             16.72                        28                                                                                   ##STR37##         29  186-187                                                                            68.55                                                                            6.33                                                                             15.99                                                                            68.51                                                                            6.40                                                                             16.06                        29                                                                                   ##STR38##         30  213-214                                                                            69.21                                                                            6.64                                                                             15.37                                                                            69.17                                                                            6.69                                                                             15.42                        30                                                                                   ##STR39##         26  208-210                                                                            65.79                                                                            5.84                                                                             18.05                                                                            65.90                                                                            5.69                                                                             18.08                        31                                                                                   ##STR40##         48  181-182                                                                            67.15                                                                            6.91                                                                             17.80                                                                            67.24                                                                            6.94                                                                             17.72                        32                                                                                   ##STR41##         20  175-177                                                                            66.47                                                                            6.64                                                                             18.45                                                                            66.51                                                                            6.58                                                                             18.44                        33                                                                                   ##STR42##         22  183-184                                                                            69.82                                                                            6.92                                                                             14.80                                                                            69.74                                                                            6.92                                                                             14.78                        34                                                                                   ##STR43##         36  233-234                                                                            69.82                                                                            6.92                                                                             14.80                                                                            69.78                                                                            6.87                                                                             14.85                        35                                                                                   ##STR44##         26  209-211                                                                            70.75                                                                            6.71                                                                             14.35                                                                            70.81                                                                            6.70                                                                             14.37                        36                                                                                   ##STR45##         48  220-222                                                                            67.49                                                                            5.03                                                                             17.49                                                                            67.54                                                                            5.08                                                                             17.40                        37                                                                                   ##STR46##         23  227-228                                                                            68.55                                                                            6.33                                                                             15.99                                                                            68.48                                                                            6.27                                                                             16.04                        38                                                                                   ##STR47##          5  138-140 (dec.)                                                                     67.84                                                                            5.99                                                                             16.65                                                                            67.98                                                                            6.11                                                                             16.74                        39                                                                                   ##STR48##         37  253-254                                                                            70.38                                                                            7.19                                                                             14.27                                                                            70.38                                                                            7.21                                                                             14.33                        40                                                                                   ##STR49##         15  138-140                                                                            69.77                                                                            7.43                                                                             15.65                                                                            69.82                                                                            7.41                                                                             15.58                        41                                                                                   ##STR50##         51  198-200                                                                            68.55                                                                            6.33                                                                             15.99                                                                            68.50                                                                            6.28                                                                             15.91                        __________________________________________________________________________

                                      TABLE II                                    __________________________________________________________________________     ##STR51##                                                                    Com-                         Microanalysis                                    pound               Yield                                                                             M.p. Calc. %  Found %                                 n.  R               %   °C.                                                                         C  H  N  C  H  N                                 __________________________________________________________________________    42                                                                                 ##STR52##      50  245-247                                                                            67.84                                                                            5.99                                                                             16.65                                                                            67.82                                                                            5.94                                                                             16.70                             43                                                                                 ##STR53##      21  229-232 (dec.)                                                                     67.84                                                                            5.99                                                                             16.65                                                                            67.79                                                                            6.04                                                                             16.73                             44                                                                                 ##STR54##      41  189-191                                                                            65.74                                                                            6.34                                                                             19.16                                                                            65.88                                                                            6.22                                                                             19.15                             45                                                                                 ##STR55##      23  220-223 (dec.)                                                                     54.80                                                                            5.75                                                                             15.98                                                                            54.96                                                                            5.91                                                                             16.11                             46                                                                                 ##STR56##       6  226-227                                                                            67.84                                                                            5.99                                                                             16.65                                                                            67.77                                                                            5.93                                                                             16.64                             47                                                                                 ##STR57##      33  158-160                                                                            69.21                                                                            6.64                                                                             15.37                                                                            69.23                                                                            6.70                                                                             15.39                             __________________________________________________________________________

                                      TABLE III                                   __________________________________________________________________________     ##STR58##                                                                    Com-                         Microanalysis                                    pound               Yield                                                                             M.p. Calc. %  Found %                                 n.  R               %   °C.                                                                         C  H  N  C  H  N                                 __________________________________________________________________________    48                                                                                 ##STR59##      21  170-172                                                                            71.62                                                                            6.31                                                                             12.53                                                                            71.60                                                                            6.33                                                                             12.58                             49                                                                                 ##STR60##      51  169-170                                                                            72.18                                                                            6.63                                                                             12.02                                                                            72.26                                                                            6.54                                                                             11.95                             50                                                                                 ##STR61##      64  195-197                                                                            69.21                                                                            6.64                                                                             15.37                                                                            69.34                                                                            6.72                                                                             15.29                             51                                                                                 ##STR62##      30  152-154                                                                            73.18                                                                            7.21                                                                             11.13                                                                            73.02                                                                            7.15                                                                             10.98                             52                                                                                 ##STR63##      22  174-176                                                                            72.70                                                                            6.93                                                                             11.56                                                                            72.54                                                                            6.91                                                                             11.52                             __________________________________________________________________________

The antisecretory and anticholinergic activity in the rat, the acutetoxicity in the mouse and the antimuscarinic activity, in comparisonwith pirenzepine as reference drug, have been determined on thecompounds of the invention.

Gastric acid secretion in the pylorus ligated rat

The method of Shay H., Kamarov S. A., Fels, S. S., Meranee D.,Gruenstein M., Siplet H., Gastroenterology, 5, 43 (1945) was used,slightly modified according to the following:

Male Sprague-Dawley rats weighing 150∓5 g fasting since 48 hours wereused. Pylorus ligation was performed for 4 hours. The products underexam were administered by the oral route immediately after the ligation.

Carbachole salivation in the rat

The method cited by R. Turner: "Parasympatholytic Agents" in R. Turner"Screening Methods in Pharmacology" pag. 137. Academic Press. New Yorkand London 1965, with slight changes, was used.

Male Sprague-Dawley rats, average weight 150∓5 g, fasting since 24hours, were used.

The salivation was induced by the intraperitoneal administration of 1mg/kg of carbachole.

The products under exam were administered orally one hour before thecholinergic stimulus.

Interaction with muscarinic receptor

The activity at the muscarinic receptor level was evaluated by means ofdisplacement, with different concentrations of the compounds under exam,of the ³ H-QNB bound to the receptors of the rat cerebral cortexaccording to the method, with minor changes, of H. I. Yamamura and S. H.Snyder-Proc. Nat. Acad. Sci., 71, 1725-1729 (1974).

Acute toxicity

The acute toxicity was determined by administering by oral route thesubstances under exam to Swiss mice; average weight 20∓2 g. Theobservation period was 14 days. 10 Animals were used for each testeddose.

The results are reported in the following Table IV.

                                      TABLE IV                                    __________________________________________________________________________    Pharmacological activities of the                                             compounds I                                                                                 Carbachol                                                                             Interaction                                                  % Antisecre-                                                                           salivation -                                                                          with mu-                                                Com- tory activ-                                                                            % protection                                                                          scarinic LD.sub.50                                      pound                                                                              ity mg/kg p.o                                                                          62.5 mg/kg                                                                            receptor mg/kg                                          n.   6.25                                                                             12.5                                                                             25 p.o.    10.sup.-7                                                                        10.sup.-6                                                                        10.sup.-5                                                                        p.o                                            __________________________________________________________________________    1    10.3                                                                             36.3                                                                             71.3                                                                              0      0  3.96                                                                             46.6                                                                             >500                                           2    11.6                                                                             33.7                                                                             55.2                                                                             100     12.8                                                                             49.7                                                                             93.3                                                                             >500                                           4    21.5                                                                             50.2                                                                             64.1                                                                             50      3.0                                                                              54.3                                                                             94.4                                                                             <500                                           5    18.7                                                                             58.4                                                                             66.7                                                                             100     14.6                                                                             71.7                                                                             96.9                                                                             <500                                           6     7.2                                                                             25.8                                                                             51.4                                                                             10      7.5                                                                              43.9                                                                             85.5                                                                             <500                                           10   12.4                                                                             24.7                                                                             41.5                                                                              0      0  0.2                                                                              30.2                                                                             >500                                           P     7.9                                                                             46.0                                                                             71.5                                                                             10      12.8                                                                             57.4                                                                             90.5                                                                              >2000                                         __________________________________________________________________________     P = Pirenzepine.                                                         

The present invention refers also to all the industrially applicableaspects connected with the use of compounds I in therapy.

An essential aspect of the invention is therefore provided bypharmaceutical compositions, suitable for the oral, parenteral ortopical administration, containing as the active principle at least oneof the compounds of formula I or one of pharmaceutically acceptablesalts thereof in addition to the carriers usually employed inpharmaceutical technique.

Examples of said compositions are provided by capsules, sugar-coatedtablets, tablets, syrups, drops, ointments, sterile vials for injectionetc.

We claim:
 1. A compound of the formula: ##STR64## in which: R₁ is H or CH₃ n is 0, 1 or 2when: n is 0 m represents a nitrogen cyclic group selected from: ##STR65## when: n is 1 and R₁ is H M represents a nitrogen cyclic group selected from: ##STR66## in which: R₄ is H, CH₃ or C₂ H₅ R₅ is --COOH, --COOCH₃, --COOC₂ H₅ or ##STR67## R₆ is acetyl, phenyl, cyclopropyl, CH₂ --CH₂ OH, CH₂ --CH₂ --CH₂ OH, ##STR68## --COOC₂ H₅ or ##STR69## R₇ is H or CH₃ when: n is 1 and R₁ is CH₃ M represents a nitrogen cyclic group selected from: ##STR70## in which: R₄ is H, CH₃ or C₂ H₅ when: n is 2 and R₁ is H M represents a nitrogen cyclic group selected from: ##STR71## in which: R₄ is H, CH₃ or C₂ H₅.
 2. A compound according to claim 1 in which n is
 0. 3. A compound according to claim 2 in which the compound is 11-[(1-methyl-piperidine-4-yl)-carbonyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]-benzodiazepine-5-one.
 4. A compound according to claim 2 in which the compound is 11-[(1-methyl-piperidine-3-yl)-carbonyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]-benzodiazepine-5-one.
 5. A compound according to claim 1 in which n is
 1. 6. A compound according to claim 5 in which the compound is 11-[(2-methyl-pyrrolidin-1-yl)-acetyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]-benzodiazepine-5-one.
 7. A compound according to claim 5 in which the compound is 11-[2-(4-methyl-piperazine-1-yl)-propionyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]-benzodiazepine-5-one dihydrochloride.
 8. A compound according to claim 1 in which n is
 2. 9. A compound according to claim 8 in which the compound is 11-[3-(4-methyl-piperazine-1-yl)-propionyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]-benzodiazepine-5-one.
 10. A compound according to claim 8 in which the compound is 11-[3-(2-methyl-piperidine-1-yl)-propionyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-5-one.
 11. A pharmaceutical composition having antisecretory, antiulcer, antimuscarinic and spasmolytic activity which comprises as the principal active ingredient an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.
 12. A pharmaceutical composition according to claim 11 in which the principal active ingredient is 11-[(1-methylpiperidine-4-yl)-carbonyl]-6,11-dihydro-5H-pyrido[2,3-b][1,5]-benzodiazepine-5-one. 